MiR-4303 relieves chondrocyte inflammation by targeting ASPN in osteoarthritis

Abstract Background Osteoarthritis (OA) is a severe articular cartilage disease whose pathogenesis involves the inflammation of chondrocytes. MicroRNAs (miRNAs) are considered to be effective inflammation regulators. However, the regulatory mechanism of miRNAs in osteoarthritis needs to be further elucidated. In this paper, we aim to investigate the underlying mechanisms by which miR-4303 regulates osteoarthritis. Methods RT-qPCR is performed to detect the levels of miR-4303, ASPN, PDIA3, PIK3CA, and TRAF3; CCK-8 assay is conducted to evaluate chondrocyte viability; EdU assay was carried to assess chondrocyte proliferation; western blot is conducted to measure the levels of ASPN, PCNA, Ki-67, CyclinA1, CyclinB1, CyclinD2, p27, Bax, Bcl-2, cleaved caspase-3, and Cleaved caspase-9 proteins; FACs is performed to detect the distribution of chondrocytes in each cell cycle and chondrocyte apoptosis; ELISA is conducted to assess the levels of TNF-β, IL-1β and IL-6 in the supernatant of chondrocytes; the potential binding sites of miR-4303 and ASPN are predicted by miRDB software, which is confirmed by the dual-luciferase reporter gene assay. Results Our findings illustrated that miR-4303 was down-regulated in arthritic tissues and LPS-induced chondrocytes; miR-4303 overexpression rescued LPS-induced chondrocyte viability, proliferation and cell cycle and alleviated LPS-induced chondrocyte apoptosis; miR-4303 overexpression inhibited the release of inflammatory factors in LPS-induced chondrocytes; miR-4303 targeted ASPN and miR-4303 relieved chondrocyte inflammation via targeting ASPN. Conclusion MiR-4303 serves as a prognostic biomarker and relieves chondrocyte inflammation via targeting ASPN. Our findings provide novel prognostic biomarkers in predicting the progression and prognosis of osteoarthritis.